Studies directed towards the total synthesis of prostaglandins

Abstract

During the last two decades significant developments have been made in the chemistry of prostaglandins. New routes of synthesis to the naturally occurring prostaglandins, as well as various analogues, have been described. In parallel to these synthetic achievements, progress has also been made in biology, in particular with the discovery of new receptor, subtypes and/or isoforms. At the interface of both domains, new molecules have been prepared which proved to be valuable as pharmacological tools. On the other hand, SAR studies on prostaglandin analogues paved the way towards new and more selective drugs in various areas of medicinal chemistry. Therefore, taking into account the importance of prostanoids in human biology, it is clearly expected that strong developments will be continuing in the future both in chemistry and in biology. newlineIn view of significant potential displayed by PG?s in various therapeutic actions, the author has developed a general synthesis of ophthalmic prostaglandins (Anti-glaucoma agents) and their analogues and the details are described in five chapters of the thesis. newlineThe first chapter presents the general introduction on prostaglandins (PGs), Chapter-2 deals with the synthesis of a versatile key intermediate (148), (±) (Z)-4-formyl-5-(7-isopropoxy-7-oxohept-2-enyl)cyclopentane-1,3-diyldibenzoate from racemic Corey lactone (140) which can be elaborated into several clinical ophthalmic prostaglandins viz., Latanoprost, Bimatoprost and Travoprost. Chapter-3 describes the details on the synthesis the of Bimatoprost and its analogues from key intermediate (148), Chapter-4 consists of details of the syntheses of Travoprost and its analogues from key intermediate (148) and Chaper-5 comprises the details on synthesis of structural analogs for Latanoprost from key intermediate (148). 1.0 Chapter 1: Introduction of Prostaglandins (PGs) This chapter describes about introduction of prostaglandins (PGs), structure of PGs, nomenclature, important physiological actions, prostaglandins receptors.